Xanthine oxidase (XO) and sulfite oxidase (SO) are mononuclear molybdenum enzymes found in humans that have been linked to Lesch-Nyhan syndrome and sulfite oxidase deficiency, respectively. Both of these diseases are genetic disorders that cause significant neurological defects and ultimately death. XO has also been implicated in oxidative injury as occurs following ischemic shock. Consensus structures derived from EXAFS and crystallographic studies have allowed for new and more detailed hypotheses to be put forth concerning the mechanism of these enzymes. The following testable hypotheses will be specifically addressed: (i) The O-Mo-Cys(S)-C dihedral angle in sulfite oxidase (SO) plays a critical role in modulating the reduction potential of the active site and in facilitating oxygen atom transfer (OAT). (ii) In addition to coupling the active site of SO info efficient sigma-mediated pathways for electron transfer the ene-1,2-dithiolate plays a pivotal role in selecting and activating the equatorial oxo group for atom transfer. Charge redistribution within the ene-1,2-dithiolate effectively facilitates sequential isopotential one-electron transfers. (iii) Conversion of the catalytically essential [MoVIOS(SH)]+ unit to [MoIVO(SH)]+ upon hydroxylation occurs via formal hydride transfer in the XO family of enzymes and is a necessary prerequisite for coupling the active site into efficient superexchange pathways for electron transfer involving the o-orbitals of the pyranopterin. The proposed experiments involve a combination of biochemical manipulation and synthetic chemistry to prepare samples for spectroscopic study.